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H Wollmann

Publications and source records attributed to H Wollmann.

At least 19 recordsLinked to original sources
PubMed2006

The d3/fl-growth hormone (GH) receptor polymorphism does not influence the effect of GH treatment (66 microg/kg per day) or the spontaneous growth in short non-GH-deficient small-for-gestational-age children: results from a two-year controlled prospective study in 170 Spanish patients.

CONTEXT: The d3/fl-GH receptor (d3/fl-GHR, exon 3-deleted/full-length GHR) has recently been associated with responsiveness to GH therapy. OBJECTIVE: The objective of the study was to evaluate whether the d3/fl-GHR genotypes influence the intensity of spontaneous and/or GH therapy-stimulated growth in small-for-gestational-age (SGA) patients. DESIGN: This was a 2-yr prospective, controlled, randomized trial. SETTING: Thirty Spanish hospitals participated. Auxologic and GH secretion evaluation was hospital based, whereas molecular analyses and auxologic data computation were centralized. PATIENTS: Patients included 170 short SGA children: 140 remained prepubertal and 30 entered puberty during the second follow-up year. INTERVENTION: Eighty-six were treated with GH (66 microg/kg.d) for 2 yr and 84 were not treated. MAIN OUTCOME MEASURES: Previous and 2-yr follow-up auxologic data were recorded at each hospital, d3/fl-GHR genotypes determined, and data analyzed for patients who remained prepubertal (group 1, 68 GH treated and 72 non-GH treated) and for all the patients (group 2). RESULTS: In group 1 GH-treated patients, growth velocity, and height-sd score during the first and second years, total 2-yr height gain (18.5 +/- 2.4 cm in d3/d3; 18.4 +/- 2.6 in d3/fl; 19.5 +/- 2.3 in fl/fl), Delta 2-yr height increase (9.1 +/- 2.4 cm in d3/d3; 9.4 +/- 3.0 in d3/fl; 10.4 +/- 2.1 in fl/fl), first-year growth prediction and studentized residual values (0.08 +/- 1.26 in d3/d3; 0.28 +/- 1.21 in d3/fl; 0.67 +/- 0.95 in fl/fl) did not differ among the d3/fl-GHR genotypes. In group 1 non-GH-treated patients, neither growth velocity nor height-sd score changed significantly, and values were similar in each d3/fl-GHR genotype. Results in all patients (group 2) were similar to those in group 1. CONCLUSIONS: In short non-GH-deficient SGA children, both spontaneous growth rate and responsiveness to 66 microg/k.d GH therapy were similar for each d3/fl-GHR genotype carried.

Body Height↗
PubMed2001

[Uniparental disomy 7 in the pathogenesis of Silver-Russell syndrome].

The authors report the frequency and the clinical signs of uniparental disomy of chromosome 7 in Silver-Russell syndrome patients. A cohort of 73 families were typed with Short Tandem Repeat markers from chromosomes 7. In 6 patients maternal uniparental disomy 7 (UPD7) was detected. Summarising their data and those from the literature, an overall frequency of maternal uniparental disomy 7 of approximately 10% can be estimated. Allelic distribution in two of their maternal uniparental disomy 7 families indicates complete isodisomy whereas allelic patterns in the other four families are consistent with partial and complete heterodisomy, respectively. The clinical features of maternal uniparental disomy 7 patients do not show any deviation from the non-uniparental disomy 7 patients. Additionally, there was not hint for possible influences of iso- or heterodisomy, possibly associated with different stages of mosaicism. Their results demonstrate the necessity to screen SRS patients for UPD7 although the effect of UPD7 cannot be correlated to the SRS phenotype yet. Furthermore, an association between UPD for chromosomes other than 7 and SRS seems to be negligible. Vice versa, maternal UPD7 is not detectable in non-SRS patients. Therefore, testing for maternal UPD7 can be restricted to SRS families, searching for other UPDs in this population does not seem to be reasonable. Additionally, cytogenetic analysis should also be performed in SRS patients: identification of commonly involved chromosomal regions should allow narrowing down a SRS-relevant region.

Abnormalities, Multiple↗
PubMed2000

X-linked congenital adrenal hypoplasia: new mutations and long-term follow-up in three patients.

Mutations of the DAX-1 gene, which encodes a newly discovered member of the nuclear hormone receptor family, were reported to cause X-linked congenital adrenal hypoplasia and hypogonadotrophic hypogonadism. While genetic data on DAX-1 are accumulating, information on the clinical course of the disorder are scarce. Here we present a detailed documentation of longitudinal data relating to three cases. We retrospectively collected clinical data on three boys (6, 14 and 14.5 years old) who we examined over a period ranging between 5 and 14 years. Mutational analysis of the DAX-1 gene was performed by means of direct sequencing of PCR products. The patients presented at ages between 4 and 6 weeks with salt-wasting, but there was no evidence of hypoglycaemia. All three cases were initially erroneously diagnosed with isolated aldosterone deficiency. Glucocorticoid deficiency was established by means of ACTH stimulation tests at 4 months, 3 and 13 years of age. One boy, whose therapy was discontinued at the age of 4 months, developed normally until adrenal crisis occurred at the age of 13 years. In all three cases, congenital hypogonadism was ruled out during infancy, as penis size was normal, the testes were descended, and serum samples contained normal testosterone levels. One boy exhibited transient hypergonadotrophism at age 9 but showed no clinical signs of puberty or an increase in serum testosterone. Onset of puberty and LHRH tests proved to be normal in his case as well as in another patient studied. In two patients, genetic analysis revealed new mutations at the C-terminus of DAX-1, these being a 1-base deletion (656delG) inherited from the mother and a de-novo 2-base insertion (728insCA) of the DAX-1 gene, respectively, both causing frame shift and premature stops at codons 263 and 398. One boy was affected by a new nonsense mutation of codon 39 (W39X) inherited from his mother. Mineralocorticoid deficiency preceded glucocorticoid deficiency which could be diagnosed through ACTH stimulation after the neonatal period. Transitory functional recovery of the adrenal glands can occur in adrenal hypoplasia congenita (AHC). Transient hypergonadotrophism may be one of the first indicators of defects in the gonadal axis, although normal initiation of puberty is not rare. The definitive diagnosis was established by means of molecular analysis of the DAX-1 gene. There was no correlation between types of mutations and phenotypes. The diagnostic procedure in male children and adolescents presenting with adrenal crisis should include ACTH stimulation tests and mutational analysis of DAX-1 in the absence of another proven aetiology.

Adolescent↗
PubMed1999

A rapid screening for steroid 21-hydroxylase mutations in patients with congenital adrenal hyperplasia. Mutations in brief no. 247. Online.

Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia (CAH). CAH due to 21-hydroxylase deficiency is divided into three classes: salt-wasting (classical), non-classical and simple virilizing, reflecting different degrees of clinical severity. Using polymerase chain reaction (PCR) and allele-specific oligonucleotide hybridisation (ASO), we screened the DNA of 62 Caucasian CAH families (heterozygous parents and children) for 14 different and frequently-found CYP21-mutations (HGMD). Of the 62 patients (21 males, 41 females), 26 females and 11 males had the classical or salt-wasting form, 3 females and 1 male had the non-classical form and 14 females and 7 males had simple virilizing CAH. More than 60% of the patients were compound-heterozygous. We found the mutations on 110 alleles (out of 124 alleles). There were 30 CYP21 gene deletions/conversions, 3 substitutions (P30L) in exon 1, 30 splice mutations (c.93-13A/C>G) in intron 2, 26 point mutations (I172N) in exon 4, one cluster of mutations (I236N, V237E, M239K) in exon 6, 8 mutations (V281L and 1760-1761insT) in exon 7, and 8 nonsense (Q318X) and 4 missense (R356W) mutations in exon 8. Our study supports the case for using this rapid technique for CAH-family screening as long as alleles from both affected patients and parents are screened in parallel.

Adrenal Hyperplasia, Congenital↗
PubMed1993

[The role of melatonin in growth of malignant choroid melanoma].

Increasing evidence of the immunomodulatory and tumor-depressing effects of melatonin prompted us to study altered concentrations of this multifunctional pineal hormone in the aqueous humor of eyes with melanoma. Eyes undergoing cataract surgery served as controls. First, RIA was used for the detection of melatonin (5 melanoma and 8 control eyes). In a second series we used ELISA with a newly developed antibody (6 melanoma and 11 control eyes). Moreover, the supernatant media of cultured melanomas were investigated for melatonin. We cautiously interpret the results as follows: (1) in the morning melatonin is detectable in the human aqueous humor at a concentration of ca. 35 pg/ml; (2) as blood serum and aqueous humor levels did not correlate, melatonin is probably actively secreted by the ciliary body rather than passively filtrated; (3) there are no significant changes in melatonin concentration in the aqueous humor of melanoma eyes; this, however, does not mean that melatonin does not play a role in uveal melanoma growth; (4) cultured uveal melanoma cells can probably synthesize melatonin.

Aqueous Humor↗
PubMed1990

[Computer-aided differential thermal analysis of drugs].

An open-loop on-line computer connection to a DTA apparatus of high time constant and the developed software for data acquisition and utilization are described. The new system was calibrated thermomentrically and calorically. The main aim is a enhanced purity estimation, especially by using of the modified Van't Hoff equation based on DTA curves, which first must be transformed to process-power-curves. Computer aided DTA provides utilization of higher quality and makes them faster and more exactly. Plotting of DTA curves which are baseline corrected and constructed as mean of equal curves as well as zooming are powerful and essential tools in optical comparison. The better estimation of the baseline under the peak and the computation of process-power-curve from DTA curve enable estimations based on curves of DTA apparatus' with high time constant as like as bases on DSC-curves.

Computers↗
PubMed1989

Monoamine oxidase inhibition by phenelzine and brofaromine in healthy volunteers.

The two monoamine oxidase (MAO) inhibitors phenelzine and brofaromine given for 2 to 3 weeks were compared in six volunteers. Blood pressure sensitivity to intravenous tyramine increased 2.6-fold during phenelzine (60 mg/day) and 4.8-fold during brofaromine, whereas sensitivity to oral tyramine increased more during phenelzine (15.7-fold vs 8.5-fold). After withdrawal of phenelzine, pressor sensitivity to oral tyramine returned to control values within 2 and for more than 8 weeks. Relative bioavailability of conjugated tyramine was elevated sixfold by brofaromine and 11.6-fold by phenelzine. Urinary elimination of tryptamine increased during phenelzine and brofaromine to 12.7-fold and threefold, respectively. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA) excretion decreased during brofaromine significantly by 72% and 49%, respectively. The nonsignificant decrease of MHPG excretion and the increase of intravenous tyramine pressor sensitivity caused by phenelzine are significantly related. The data suggest that the selective reversible MAO-A inhibitor brofaromine has a larger therapeutic safety than phenelzine.

Adult↗
PubMed1988

[The stability of norepinephrine hydrogen tartrate, epinephrine hydrogen tartrate and isoprenaline sulfate. 29. The stability of drugs and preparations].

Stability testing of derivatives of brenzcatechine [norepinephrine hydrogentartrate (1), epinephrine hydrogentartrate (2), isoprenaline sulfate (3)] was carried out by stress investigation storing them at different temperatures. Substances of different charges which had been stored under normal conditions were analyzed. After a period of induction all three substances had been decomposed with a higher velocity. The order of kinetic process could not be determined. The storage life time was calculated by the aid of nonlinear regression. Time limit for storage of 5 years for 1 and 2 were confirmed. We suggest to extend it for 3 to 10 years.

Drug Stability↗
PubMed1987

Influence of oestradiol on alpha 2-adrenoceptor binding sites on intact platelets of young male volunteers.

The specific binding (Bmax) of (3H-methyl)yohimbine to alpha 2-adrenoceptor binding sites on intact platelets was increased by 43% in 6 out of 7 young male volunteers 4 days after a single i.m. injection of 10 mg sustained release oestradiol, and it had returned to the starting value 4 weeks after drug administration. Mean plasma oestradiol was 331 pg/ml on Day 4 and it was within the pre-treatment control range of 19 pg/ml 4 weeks after the injection. A close correlation between the post-injection plasma oestradiol concentration and the increase in alpha 2-adrenoceptor binding sites on intact platelets was not found.

Adult↗
PubMed1987

[Stability test of trituratio paraoxoni AB-DDR 78].

Trituratio Paraoxoni was stored at various high temperatures and the content of the intact active ingredient was determined in suitable duration periods. The degradation of paraoxon follows up to 25% first order reaction. The reaction equilibrium constant calculated produces an Arrhenius-plot. The extrapolation of the reaction equilibrium constant to 20 degrees C was done under consideration of weighting factors and included a different number of loading temperatures and measurements of the concentration per time period. The shelf use calculated corresponds to the results of long-range storage. The necessity of an assaying as prescribed by AB-DDR 78 is confirmed.

Chemical Phenomena↗